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排序方式: 共有397条查询结果,搜索用时 15 毫秒
1.
Fibulin-5/DANCE is essential for elastogenesis in vivo. 总被引:19,自引:0,他引:19
Tomoyuki Nakamura Pilar Ruiz Lozano Yasuhiro Ikeda Yoshitaka Iwanaga Aleksander Hinek Susumu Minamisawa Ching-Feng Cheng Kazuhiro Kobuke Nancy Dalton Yoshikazu Takada Kei Tashiro John Ross Jr Tasuku Honjo Kenneth R Chien 《Nature》2002,415(6868):171-175
The elastic fibre system has a principal role in the structure and function of various types of organs that require elasticity, such as large arteries, lung and skin. Although elastic fibres are known to be composed of microfibril proteins (for example, fibrillins and latent transforming growth factor (TGF)-beta-binding proteins) and polymerized elastin, the mechanism of their assembly and development is not well understood. Here we report that fibulin-5 (also known as DANCE), a recently discovered integrin ligand, is an essential determinant of elastic fibre organization. fibulin-5-/- mice generated by gene targeting exhibit a severely disorganized elastic fibre system throughout the body. fibulin-5-/- mice survive to adulthood, but have a tortuous aorta with loss of compliance, severe emphysema, and loose skin (cutis laxa). These tissues contain fragmented elastin without an increase of elastase activity, indicating defective development of elastic fibres. Fibulin-5 interacts directly with elastic fibres in vitro, and serves as a ligand for cell surface integrins alphavbeta3, alphavbeta5 and alpha9beta1 through its amino-terminal domain. Thus, fibulin-5 may provide anchorage of elastic fibres to cells, thereby acting to stabilize and organize elastic fibres in the skin, lung and vasculature. 相似文献
2.
Summary Contrary to Srdi and Gloor's report, we find crystal cells (cc) in the lymph glands ofD. melanogaster larvae; the size and number of inclusions in the cc cannot be used to distinguish the 2 sibling species,D. melanogaster andD. simulans; cc in the hemocoel are not phagocytic cells; the surface properties of the lamellocytes are consistent with their derivation from plasmatocytes and not cc.Supported by grant No. CA16619 awarded by the National Cancer Institute, DHEW, USPHS. 相似文献
3.
运用最新提出的麦克斯韦电路理论,分析T形线的散射电流,将该结构等效为LC电路,求解与之对应的微分方程,得到该结构的散射电流,数值实验分别计算了T形线的等效电路参数L,C,α,β,以及相应的散射电流,分析结果表明,所得电路参数和散射电流符合物理现象,并且与矩量法的结果以及相关文献中的结果均吻合,从而证明了该方法的正确性和... 相似文献
4.
Roberts AE Araki T Swanson KD Montgomery KT Schiripo TA Joshi VA Li L Yassin Y Tamburino AM Neel BG Kucherlapati RS 《Nature genetics》2007,39(1):70-74
Noonan syndrome, the most common single-gene cause of congenital heart disease, is characterized by short stature, characteristic facies, learning problems and leukemia predisposition. Gain-of-function mutations in PTPN11, encoding the tyrosine phosphatase SHP2, cause approximately 50% of Noonan syndrome cases. SHP2 is required for RAS-ERK MAP kinase (MAPK) cascade activation, and Noonan syndrome mutants enhance ERK activation ex vivo and in mice. KRAS mutations account for <5% of cases of Noonan syndrome, but the gene(s) responsible for the remainder are unknown. We identified missense mutations in SOS1, which encodes an essential RAS guanine nucleotide-exchange factor (RAS-GEF), in approximately 20% of cases of Noonan syndrome without PTPN11 mutation. The prevalence of specific cardiac defects differs in SOS1 mutation-associated Noonan syndrome. Noonan syndrome-associated SOS1 mutations are hypermorphs encoding products that enhance RAS and ERK activation. Our results identify SOS1 mutants as a major cause of Noonan syndrome, representing the first example of activating GEF mutations associated with human disease and providing new insights into RAS-GEF regulation. 相似文献
5.
Low beta diversity of herbivorous insects in tropical forests 总被引:1,自引:0,他引:1
Novotny V Miller SE Hulcr J Drew RA Basset Y Janda M Setliff GP Darrow K Stewart AJ Auga J Isua B Molem K Manumbor M Tamtiai E Mogia M Weiblen GD 《Nature》2007,448(7154):692-695
Recent advances in understanding insect communities in tropical forests have contributed little to our knowledge of large-scale patterns of insect diversity, because incomplete taxonomic knowledge of many tropical species hinders the mapping of their distribution records. This impedes an understanding of global biodiversity patterns and explains why tropical insects are under-represented in conservation biology. Our study of approximately 500 species from three herbivorous guilds feeding on foliage (caterpillars, Lepidoptera), wood (ambrosia beetles, Coleoptera) and fruit (fruitflies, Diptera) found a low rate of change in species composition (beta diversity) across 75,000 square kilometres of contiguous lowland rainforest in Papua New Guinea, as most species were widely distributed. For caterpillars feeding on large plant genera, most species fed on multiple host species, so that even locally restricted plant species did not support endemic herbivores. Large plant genera represented a continuously distributed resource easily colonized by moths and butterflies over hundreds of kilometres. Low beta diversity was also documented in groups with differing host specificity (fruitflies and ambrosia beetles), suggesting that dispersal limitation does not have a substantial role in shaping the distribution of insect species in New Guinea lowland rainforests. Similar patterns of low beta diversity can be expected in other tropical lowland rainforests, as they are typically situated in the extensive low basins of major tropical rivers similar to the Sepik-Ramu region of New Guinea studied here. 相似文献
6.
Zhang F Wang LP Brauner M Liewald JF Kay K Watzke N Wood PG Bamberg E Nagel G Gottschalk A Deisseroth K 《Nature》2007,446(7136):633-639
Our understanding of the cellular implementation of systems-level neural processes like action, thought and emotion has been limited by the availability of tools to interrogate specific classes of neural cells within intact, living brain tissue. Here we identify and develop an archaeal light-driven chloride pump (NpHR) from Natronomonas pharaonis for temporally precise optical inhibition of neural activity. NpHR allows either knockout of single action potentials, or sustained blockade of spiking. NpHR is compatible with ChR2, the previous optical excitation technology we have described, in that the two opposing probes operate at similar light powers but with well-separated action spectra. NpHR, like ChR2, functions in mammals without exogenous cofactors, and the two probes can be integrated with calcium imaging in mammalian brain tissue for bidirectional optical modulation and readout of neural activity. Likewise, NpHR and ChR2 can be targeted together to Caenorhabditis elegans muscle and cholinergic motor neurons to control locomotion bidirectionally. NpHR and ChR2 form a complete system for multimodal, high-speed, genetically targeted, all-optical interrogation of living neural circuits. 相似文献
7.
International Consortium for Blood Pressure Genome-Wide Association Studies Ehret GB Munroe PB Rice KM Bochud M Johnson AD Chasman DI Smith AV Tobin MD Verwoert GC Hwang SJ Pihur V Vollenweider P O'Reilly PF Amin N Bragg-Gresham JL Teumer A Glazer NL Launer L Zhao JH Aulchenko Y Heath S Sõber S Parsa A Luan J Arora P Dehghan A Zhang F Lucas G Hicks AA Jackson AU Peden JF Tanaka T Wild SH Rudan I Igl W Milaneschi Y Parker AN Fava C Chambers JC Fox ER Kumari M Go MJ van der Harst P Kao WH 《Nature》2011,478(7367):103-109
Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140?mm?Hg systolic blood pressure or ≥90?mm?Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention. 相似文献
8.
Bivona TG Hieronymus H Parker J Chang K Taron M Rosell R Moonsamy P Dahlman K Miller VA Costa C Hannon G Sawyers CL 《Nature》2011,471(7339):523-526
Human lung adenocarcinomas with activating mutations in EGFR (epidermal growth factor receptor) often respond to treatment with EGFR tyrosine kinase inhibitors (TKIs), but the magnitude of tumour regression is variable and transient. This heterogeneity in treatment response could result from genetic modifiers that regulate the degree to which tumour cells are dependent on mutant EGFR. Through a pooled RNA interference screen, we show that knockdown of FAS and several components of the NF-κB pathway specifically enhanced cell death induced by the EGFR TKI erlotinib in EGFR-mutant lung cancer cells. Activation of NF-κB through overexpression of c-FLIP or IKK (also known as CFLAR and IKBKB, respectively), or silencing of IκB (also known as NFKBIA), rescued EGFR-mutant lung cancer cells from EGFR TKI treatment. Genetic or pharmacologic inhibition of NF-κB enhanced erlotinib-induced apoptosis in erlotinib-sensitive and erlotinib-resistant EGFR-mutant lung cancer models. Increased expression of the NF-κB inhibitor IκB predicted for improved response and survival in EGFR-mutant lung cancer patients treated with EGFR TKI. These data identify NF-κB as a potential companion drug target, together with EGFR, in EGFR-mutant lung cancers and provide insight into the mechanisms by which tumour cells escape from oncogene dependence. 相似文献
9.
10.
C. Rose Broome 《西北部美国博物学家》2011,41(2)
An expression of Centaurium namophilum (Gentianaceae), long confused with C. exaltatum in the Great Basin of the western United States, is described and designated as var. nevadense. It may be separated from the Death Valley region endemic, var. namophilum, by its broader leaves, its diffuse corymbose cyme, the ultimate peduncles that are longer than the flowers, its medium to deep rose pink corolla, and its stamens that equal or exceed the style and are only slightly exserted from the corolla-tube. The var. nevadense occurs from eastern California to western Utah, and from southeastern Oregon and adjacent Idaho south to the northern Mojave Desert of southeastern California. Centaurium exaltatum may be distinguished from the new variety by its broader, more elliptical leaves, dichotomous peduncles, paler pink or bluish and generally four-merous flowers, shorter and more blunt corolla lobes, and a thicker, more included style and stigma. 相似文献